Effects of nitric oxide synthase inhibitors in attenuating nicotine withdrawal in rats

This study evaluates the effects of three nitric oxide synthase (NOS) inhibitors (L-NNA, L-NAME, L-NMMA) in attenuating the precipitated nicotine withdrawal syndrome in rats. Male albino Wistar rats were made dependent on nicotine by subcutaneous infusion of nicotine (9.0 mg/kg/day) via a 7 day osmotic pump, whereas control rats received saline via osmotic pumps. Test doses of each NOS inhibitor were administered 30 min prior to mecamylamine (1 mg/kg) challenge in control and test rats on the 7th day. Somatic signs of withdrawal were scored for 15 min by using the global Gellert-Holtzman rating scale followed by a measurement of motor activity. A comparison of NOS inhibitors treated rats with the mecamylamine-precipitated nicotine rats showed that at highest dose L-NNA appears to produce a more complete attenuation of all aspects of withdrawal syndrome. On the other hand, L-NAME appears to do so both at moderate and highest doses. This could be due to an incomplete reversal of some signs of withdrawals by L-NMMA. However, motor activity increased in nicotine dependent rats with the administration of NOS inhibitors. This study demonstrates that NO plays an important role in the expression of behavioral signs of nicotine withdrawal syndrome and suggests a potential use of NOS inhibitors as an aid in tobacco smoking cessation.